The cardiovascular burden of end-stage renal disease patients.

Patients with end-stage renal disease are 10 to 20 times more at risk of cardiovascular death than the general population. Traditional cardiovascular risk factors are not able to explain the increase in the onset of cardiovascular diseases in dialysis patients. Some of the most important non traditional risk factors in uremic patients are: the inflammatory state of the patients, cytokines and growth factors, hyperhomocysteinemia, the presence of alterations of the calcium phosphorous product which can already be in progress when the glomerular filtration rate decreases to less than 60 mL/min. Clinically, these alterations cause vascular calcifications, calcifications of the heart valves and calcific uremic arteriolopathy or calciphylaxis. The pathogenesis of vascular calcification is complex and cannot be assigned to a simple, passive process: in fact, it includes factors which promote or inhibit calcification. In turn, these pathologic conditions have been found to be highly predictive of general and cardiovascular death. Given the serious clinical consequences that vascular calcifications can cause, it is necessary to carry out an early mapping of the traditional and non traditional risk factors of uremic patients as it seems that therapeutic interventions aimed at reducing or inverting the calcification process can improve the outcome of patients, above all when they are started quickly.

[Preventing and reducing comorbidity in candidates for kidney transplantation for the improvement of post-operative results]. / Prevenire e ridurre le comorbilita' nei candidati al trapianto di rene per migliorare i risultati post-trapianto.

The correct and constant management of transplant waiting lists is necessary for the optimal utilization of the limited number of organs available for transplantation. The guidelines regarding placement on transplant waiting lists (absolute and relative contraindications) are well documented, even though they are in constant development. The criteria for the monitoring of patients on waiting lists, however, are not so well defined; this aspect is subject to careful evaluation on account of the widening of the criteria for transplantation suitability, the increase in the average age of patients, a rise in the number of enrolments and, as a result, prolonged waiting time (in Italy, the average time spent on a waiting list is 37 months). During the waiting period, a greater risk of clinically significant comorbidities and mortality, above all from cardiovascular events, has been noted (the annual mortality is 5-7% in the US, 1.3% in Italy). An in-depth clinical and instrumental study of patients with chronic renal failure is necessary when screening eligible candidates for transplant programs, individualizing therapeutic strategies, and identifying patients for whom the risks outweigh the potential benefits. Clinical and instrumental monitoring, as well as adequate treatment of comorbidities during the waiting period, can help improve the post-transplant outcome. This work examines the study algorithms and monitoring procedures for patients on kidney transplant waiting lists.

[Factors determining cardiovascular disease progression after kidney transplant]. / I fattori di progressione della malattia cardiovascolare dopo trapianto renale.

Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient.

Predictive factors in chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is characterized by progressive renal dysfunction leading in many cases to graft loss. The pathogenesis of CAN involves both immune and nonimmune factors. Concerning immune factors, one of the most remarkable predictors of CAN is acute rejection, which is associated with a worse prognosis if there are multiple episodes or when late onset occurs. Delayed graft function is also a major risk factor for CAN because of a correlation between late restoration of renal function after transplantation and long-term decreased graft survival. High creatinine levels at 6 months and 1 year after transplantation, proteinuria, viral infections, and cardiovascular risk factors are additional significant parameters for the development of CAN. Recent findings suggest that a high renal segmental arterial resistance index measured by Doppler ultrasonography in intrarenal vessels is associated with poor allograft function. Moreover, the study of patient genetic profile represents a new approach to identify predictive factors for CAN.

[Therapy strategies in the prevention of chronic allograft nephropathy]. / Strategie terapeutiche nella prevenzione della nefropatia cronica da trapianto.

Chronic allograft nephropathy (CAN) is an anatomical and clinical alteration, characterized by proteinuria, hypertension and a progressive decline in kidney function, which begins at variable times (months, years) and can lead to the loss of the transplanted organ. CAN pathogenesis, which remains to be fully clarified, involves both immunological (early acute rejection, hyperimmunization, HLA-mismatches between donor and recipient, suboptimal immunosuppression, etc) and non-immunological factors (ischemia/reperfusion injury, reduced nephron mass, age differences between donor and recipient, dialysis time, hypertension, dislipidemia, proteinuria, etc). The possible prevention strategies for CAN consist of procedures aimed at the reduction of some potential risk factors: optimization of the conditions for organ explantation, diminution of ischemia/reperfusion injury, aggressive pharmacological treatment of acute rejection episodes, routine utilization of anti-hypertensive and hypolipidemic agents, and appropriate and rational immunosuppressive regimen. Moreover, some categories of immunosuppressive drugs, such as calcineurin inhibitors, can have a nephrotoxic effect, often regardless of therapeutic dosage. The introduction in clinical practice of novel immunosuppressive drugs with no nephrotoxicity, like mycophenolate mofetil and rapamycin, makes therapeutical strategies able to reduce the incidence of CAN feasible.